Delayed speech and language development, and Cough

Medium match MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 1; MDDGC1

Limb-girdle muscular dystrophies resulting from defective glycosylation of alpha-dystroglycan (DAG1 ) represent the mildest end of the phenotypic spectrum of muscular dystrophies collectively known as dystroglycanopathies. The limb-girdle phenotype is characterized by onset of muscular weakness apparent after ambulation is achieved; mental retardation and mild brain anomalies are variable (Balci et al., 2005; review by Godfrey et al., 2007). The most severe end of the phenotypic spectrum of dystroglycanopathies is represented by congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A; see MDDGA1, {236670}), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), and the intermediate range of the spectrum is represented by congenital muscular dystrophy-dystroglycanopathy with or without mental retardation (type B; see MDDGB1, {613155}). Genetic Heterogeneity of Limb-Girdle Muscular Dystrophy-Dystroglycanopathy (Type C)Limb-girdle muscular dystrophy due to defective glycosylation of DAG1 is genetically heterogeneous. See also MDDGC2 (OMIM ), caused by mutation in the POMT2 gene (OMIM ); MDDGC3 (OMIM ), caused by mutation in the POMGNT1 gene (OMIM ); MDDGC4 (OMIM ), caused by mutation in the FKTN gene (OMIM ); MDDGC5 (OMIM ), caused by mutation in the FKRP gene (OMIM ); MDDGC7 (OMIM ), caused by mutation in the ISPD gene (OMIM ); MDDGC9 (OMIM ) caused by mutation in the DAG1 gene (OMIM ); MDDGC12 (OMIM ), caused by mutation in the POMK gene (OMIM ); and MDDGC14 (OMIM ) caused by mutation in the GMPPB gene (OMIM ).

MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 1; MDDGC1 Is also known as muscular dystrophy, limb-girdle, type 2k;lgmd2k;lgmd2k; limb-girdle muscular dystrophy-intellectual disability syndrome

• Autosomal recessive inheritance
• Intellectual disability
• Microcephaly
• Scoliosis
• Motor delay

SOURCES: GARD NCIT MONDO EFO UMLS DOID OMIM ORPHANET SCTID

Medium match SPASTIC PARAPLEGIA 18, AUTOSOMAL RECESSIVE; SPG18

Spastic paraplegia-18 is a severe autosomal recessive neurologic disorder characterized by onset in early childhood of progressive spastic paraplegia resulting in motor disability. Most affected individuals have severe psychomotor retardation. Some may develop significant joint contractures (summary by Alazami et al., 2011 and Yildirim et al., 2011).

SPASTIC PARAPLEGIA 18, AUTOSOMAL RECESSIVE; SPG18 Is also known as intellectual disability, motor dysfunction, and joint contractures;idmdc;spg18

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Pica
• Scoliosis

SOURCES: ORPHANET MONDO GARD OMIM MESH UMLS DOID

Medium match HUNTINGTON DISEASE; HD

Huntington disease (HD) is an autosomal dominant progressive neurodegenerative disorder with a distinct phenotype characterized by chorea, dystonia, incoordination, cognitive decline, and behavioral difficulties. There is progressive, selective neural cell loss and atrophy in the caudate and putamen. Walker (2007) provided a detailed review of Huntington disease, including clinical features, population genetics, molecular biology, and animal models.

HUNTINGTON DISEASE; HD Is also known as huntington chorea;huntington chorea

• Autosomal dominant inheritance
• Seizures
• Pica
• Ataxia
• Cognitive impairment

SOURCES: ORPHANET OMIM UMLS ICD10 SCTID

Low match INTERSTITIAL LUNG AND LIVER DISEASE; ILLD

Interstitial lung and liver disease is an autosomal recessive disorder characterized by onset of respiratory insufficiency and progressive liver disease in infancy or early childhood. Pathologic examination of lung lavage is consistent with pulmonary alveolar proteinosis (summary by Hadchouel et al., 2015).

INTERSTITIAL LUNG AND LIVER DISEASE; ILLD Is also known as pulmonary alveolar proteinosis, reunion island, infantile liver failure syndrome 2, formerly;ilfs2, formerly

• Autosomal recessive inheritance
• Generalized hypotonia
• Failure to thrive
• Motor delay
• Anemia

SOURCES: OMIM MONDO

Low match COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 27; COXPD27

COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 27; COXPD27 Is also known as ;coxpd27

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: EFO MONDO UMLS OMIM ORPHANET

Low match CLASSIC PANTOTHENATE KINASE-ASSOCIATED NEURODEGENERATION

CLASSIC PANTOTHENATE KINASE-ASSOCIATED NEURODEGENERATION Is also known as nbia1, classic form; neurodegeneration with brain iron accumulation type 1, classic form; pkan, classic form

• Seizures
• Global developmental delay
• Cognitive impairment
• Spasticity
• Dysarthria

SOURCES: ORPHANET

Low match RIGID SPINE MUSCULAR DYSTROPHY 1; RSMD1

Desmin-related myopathies (DRM) are a clinically and genetically heterogeneous group of muscular disorders defined morphologically by intrasarcoplasmic aggregates of desmin (DES ), usually accompanied by other protein aggregates. Approximately one-third of DRM are caused by mutations in the desmin gene (Ferreiro et al., 2004).For other forms of DRM, see primary desminopathy (OMIM ).

RIGID SPINE MUSCULAR DYSTROPHY 1; RSMD1 Is also known as rigid spine syndrome;rss, myopathy, sepn1-related, muscular dystrophy, congenital, merosin-positive, with early spine rigidity;mdrs1, multicore myopathy, severe classic form, minicore myopathy, severe classic form, multiminicore disease, severe classic form, desmin-related myopathy with mallory bodies, muscular dystrophy, congenital, eichsfeld type

• Autosomal recessive inheritance
• Short stature
• Generalized hypotonia
• Pica
• Scoliosis

SOURCES: UMLS SCTID OMIM

Low match GAUCHER DISEASE, TYPE II

Type II Gaucher disease is an acute neuronopathic form of the disorder with onset in infancy and death often by 2 years of age. Patients are usually normal at birth, but develop hepatosplenomegaly, developmental regression, and growth arrest within a few months of age. Neurologic deterioration proceeds rapidly, with cranial nerve and extrapyramidal tract involvement (Stone et al., 2000).

GAUCHER DISEASE, TYPE II Is also known as gd ii, gaucher disease, acute neuronopathic type;acute neuronopathic gaucher disease; infantile cerebral gaucher disease

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Strabismus
• Failure to thrive

SOURCES: UMLS GARD OMIM MONDO SCTID ORPHANET DOID

Low match NEMALINE MYOPATHY 3; NEM3

Nemaline myopathy is a form of congenital myopathy characterized by abnormal thread- or rod-like structures in muscle fibers on histologic examination ('nema' is Greek for 'thread'). The clinical phenotype is highly variable, with differing age at onset and severity. Muscle weakness typically involves proximal muscles, with involvement of the facial, bulbar, and respiratory muscles (Ilkovski et al., 2001). Attempts at classification of nemaline myopathies into clinical subtypes have been complicated by the overlap of clinical features and a continuous phenotypic spectrum of disease (North et al., 1997; Wallgren-Pettersson et al., 1999; Ryan et al., 2001; Sanoudou and Beggs, 2001). In general, 2 clinical groups can be readily distinguished: 'typical' and 'severe.' Typical nemaline myopathy is the most common form, presenting as infantile hypotonia and muscle weakness. It is slowly progressive or nonprogressive, and most adults achieve ambulation. The severe form of the disorder is characterized by absence of spontaneous movement or respiration at birth, arthrogryposis, and death in the first months of life. Much less commonly, late-childhood or even adult-onset can occur. However, adult-onset nemaline myopathy is usually not familial and may represent a different disease (Wallgren-Pettersson et al., 1999; Sanoudou and Beggs, 2001).Myopathy caused by mutations in the ACTA1 gene can show a range of clinical and pathologic phenotypes. Some patients have classic rods, whereas others may also show intranuclear rods, clumped filaments, cores, or fiber-type disproportion (see {255310}), all of which are nonspecific pathologic findings and not pathognomonic of a specific congenital myopathy. The spectrum of clinical phenotypes caused by mutations in ACTA1 may result from different mutations, modifying factors affecting the severity of the disorder, variability in clinical care, or a combination of these factors (Nowak et al., 1999; Kaindl et al., 2004). Genetic Heterogeneity of Nemaline MyopathySee also NEM1 (OMIM ), caused by mutation in the tropomyosin-3 gene (TPM3 ) on chromosome 1q22; NEM2 (OMIM ), caused by mutation in the nebulin gene (NEB ) on chromosome 2q22; NEM4 (OMIM ), caused by mutation in the beta-tropomyosin gene (TPM2 ) on chromosome 9p13; NEM5 (OMIM ), also known as Amish nemaline myopathy, caused by mutation in the troponin T1 gene (TNNT1 ) on chromosome 19q13; NEM6 (OMIM ), caused by mutation in the KBTBD13 gene (OMIM ) on chromosome 15q22.31, NEM7 (OMIM ), caused by mutation in the cofilin-2 gene (CFL2 ) on chromosome 14q12; NEM8 (OMIM ), caused by mutation in the KLHL40 gene (OMIM ), on chromosome 3p22; NEM9 (OMIM ), caused by mutation in the KLHL41 gene (OMIM ) on chromosome 2q31; NEM10 (OMIM ), caused by mutation in the LMOD3 gene (OMIM ) on chromosome 3p14; and NEM11 (OMIM ), caused by mutation in the MYPN gene (OMIM ) on chromosome 10q21. Several of the genes encode components of skeletal muscle sarcomeric thin filaments (Sanoudou and Beggs, 2001).Mutations in the NEB gene are the most common cause of nemaline myopathy (Lehtokari et al., 2006).

NEMALINE MYOPATHY 3; NEM3 Is also known as ;actin myopathy

• Autosomal recessive inheritance
• Autosomal dominant inheritance
• Generalized hypotonia
• Pica
• Scoliosis

SOURCES: OMIM DOID MONDO NCIT UMLS MESH ORPHANET SCTID

Low match CEREBROCOSTOMANDIBULAR SYNDROME; CCMS

Cerebrocostomandibular syndrome (CCMS) is characterized mainly by severe micrognathia, rib defects, and mental retardation. A spectrum of rib gap defects have been reported ranging from a few dorsal rib segments to complete absence of ossification. In about half of the 65 reported cases to date, there is cerebral involvement including mental retardation, microcephaly, and histologic anomalies. Both autosomal dominant and autosomal recessive forms of the disorder have been described (Zeevaert et al., 2009).See CDG2G (OMIM ) for a cerebrocostomandibular-like syndrome.

CEREBROCOSTOMANDIBULAR SYNDROME; CCMS Is also known as rib gap defects with micrognathia;

• Autosomal recessive inheritance
• Autosomal dominant inheritance
• Intellectual disability
• Global developmental delay
• Short stature

SOURCES: ORPHANET OMIM UMLS MONDO MESH SCTID GARD